Predicting the Clinical Outcome of Lung Adenocarcinoma Using a Novel Gene Pair Signature Related to RNA-Binding Protein

Abstract EN

Adenocarcinoma is the most common type of lung cancer, and patients have varying prognoses.

RNA-binding proteins (RBP) are deemed to be closely associated with tumorigenesis and development, but the exact mechanism is currently unknown.

This study was aimed at constructing a new robust prognostic model based on RNA-binding protein-related gene pair scores for better clinical guidance.

The model for this study was constructed based on data of lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database.

Prognosis-related RBP gene pair models were created based on differentially expressed genes, and the accuracy of the models was verified in a different age, staging, and other subdatasets.

A total of 379 RNA-binding protein-related genes were differentially expressed in tumor tissue.

From these genes, we constructed a prognostic model consisting of 33 gene pairs, which were found to be significantly associated with survival in TCGA dataset (P<0.0001, hazard ratio HR=4.380 (3.139 to 6.111)) and different subdatasets.

As expected, the results were verified in the GEO validation cohort (P=7.8×10−3, HR=1.597 (1.095 to 2.325)).

We found that the signature exhibited an independent prognostic factor in both the univariate and multivariate Cox regression analyses (P<0.001).

CIBERSORT was applied to estimate the fractions of infiltrated immune cells in bulk tumor tissues.

CD8 T cells, activated dendritic cells, regulatory T cells (Tregs), and activated CD4 memory T cells presented a significantly lower fraction in the high-risk group (P<0.01).

Patients in the high-risk group had significantly higher tumor mutational burden (TMB) (P=4.953e−04) and lower levels of immune cells (P=3.473e−05) and stromal cells (P=0.005) in the tumor microenvironment than those in the low-risk group.

Furthermore, the Protein-protein interaction (PPI) network and various enrichment analyses have genuinely uncovered the interrelationships and potential functions of the RBP genes within the model.

The results of the present study validated the importance of RNA-binding proteins in tumorigenesis and progression and support the RBP gene-related signature as a promising marker for prognosis prediction in lung adenocarcinoma.